Study suggests potential genetic markers of MS-related vision loss

November 01, 2019
In a bid to determine factors linked to the most debilitating forms of multiple sclerosis, researchers say they have identified three so-called "complement system" genes that appear to play a role in MS-caused vision loss. If further studies confirm the findings, the study’s authors said they could serve as markers for monitoring and predicting progression and severity of MS. According to the researchers, this approach represents the beginning of precision medicine for MS and may ultimately allow designer therapies, as is being done for specific cancers.

For their study, researchers at Johns Hopkins Medicine used optical coherence tomography – an imaging technique that allowed the researchers to look at the back of each patient's eyes and assess damage to the nerve cells in the retina – in 374 patients with all types of MS. The patients were an average of 43 years old and mostly women.

The investigators recruited these patients and performed imaging every few years from 2010 to 2017, yielding an average of 4.6 scans per participant over the course of the study. The scans were used to measure thinning of the layer of the nerve cells – known as ganglion cells – in the retina over time. The average rate of deterioration was a loss of 0.32 micrometers of tissue per year in each patient.

Then, using blood samples from the patients to collect their DNA, the researchers hunted for genetic mutations in those people with the fastest deterioration rates and identified 23 such DNA variations that mapped to the complement gene C3.

Next, to search for genes further linked to vision loss, they performed an analysis of an existing clinical trial group of another 835 people with MS, of whom 74 percent were women, and whose average age was 40. Each participant underwent periodic vision testing about every year to distinguish their ability to detect contrast – finer and finer shades that distinguish light versus dark.

Using DNA from the blood samples of these 835 participants, the researchers identified specific genetic changes in two complement genes, C1QA and CR1, linked to those people with the most rapidly declining ability to distinguish letters with less contrast. Patients with genetic changes in the C1QA gene were 71 percent more likely to develop difficulty detecting visual contrast, whereas those with genetic changes in the CR1 gene were at 40 percent increased risk for developing a reduced ability to detect contrast.

These complement genes found to be linked with severity of MS vision loss hold the genetic instructions for making complement proteins.

The findings were reported in the journal Brain.

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